Mario Zanchetta

Antibodies to oxidized low-density lipoproteins and angiographically assessed coronary artery disease in white patients.

Background—Low-density lipoprotein (LDL) can be oxidatively modified by reactive oxygen species, thus generating oxLDL. The latter induce formation of specific antibodies (oxLDLAb), which are detectable in patients with atherosclerosis, in which they might play a pathogenic or a protective role. Thus, we aimed to investigate the association of antibodies with oxidized LDLs (oxLDL) (oxLDLAbs) with coronary artery disease (CAD) and acute coronary syndromes. Methods and Results—In a cross-sectional study of 529 consecutive patients undergoing quantitative coronary angiography for suspected CAD, we measured the titer of IgG oxLDLAbs by ELISA. With regression analysis techniques, we also investigated the determinants of oxLDLAb titer and the association of oxLDLAbs with CAD severity. We found no significant differences of oxLDLAb titer between groups of patients without and with different CAD severity. The oxLDLAb titer was 18.6 enzyme units (EU) (11.5 to 25.7 EU/mL) (mean, 95% CI) in patients without CAD; 16.8 EU (9.6 to 24.2 EU) in patients with stenosis <50%; and 19.9 EU (15 to 24.8 EU), 17.2 (13.8 to 20.6 EU), and 14.7 EU (12.1 to 17.3 EU) in those with in 1-, 2-, or 3-vessel ≥50% stenosis, respectively. Similarly, no differences of oxLDLAb titer between patients without and with acute coronary syndrome were found. The oxLDLAb titer correlated weakly with aging and with serum total, LDL, and HDL cholesterol and plasma homocysteine levels; however, only age and HDL cholesterol remained significant predictors of the oxLDLAb titer at a stepwise regression analysis. Conclusions—The results of this study, which was adequately powered from the statistical standpoint, provided no evidence for an association of IgG oxLDLAb titer with angiographically assessed CAD in whites.

Plasma Adiponectin for Prediction of Cardiovascular Events and Mortality in High-Risk Patients

CONTEXT The prognostic value of plasma levels of adiponectin, an adipocytokine with antiatherogenic, antiinflammatory, and insulin-sensitizing effects, is contentious. OBJECTIVE The objective of the study was to investigate whether plasma adiponectin levels predict cardiovascular (CV) events and mortality in high-risk coronary artery disease (CAD) patients. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURE: We measured plasma adiponectin and examined its impact on the incidence of CV deaths and events at follow-up in the context of all potentially relevant background covariates in 712 high-risk patients of the Genetic and ENvironmental factors in Coronary Atherosclerosis study who underwent coronary angiography for suspected CAD. Based on the population plasma adiponectin median (6.38 microg/ml, interquartile range 4.2-10.2), we split the patients in a high- and a low-plasma adiponectin subgroup. After a median follow-up of 3.8 years (interquartile range 3.3-4.3 yr), outcome data were obtained in 100% of the patients and 45 CV deaths (6.4%) were recorded. Kaplan-Meier analysis unexpectedly showed a higher CV death rate in high-plasma adiponectin than low-plasma adiponectin patients. By contrast, multivariate Cox regression analysis, in which potential confounders, including ongoing medical treatment, were considered, showed no impact of plasma adiponectin on CV death. Similar negative results were obtained using the propensity score that considered all relevant covariables and medical treatment rate, which differed between the high- and low-plasma adiponectin group. CONCLUSIONS In high-risk CAD patients, plasma adiponectin above the median (6.38 microg/ml) implies a paradoxical higher risk of CV death. However, when relevant covariates that differ between high- and low-plasma adiponectin groups are considered, this association wanes, indicating that the clustering of plasma adiponectin with other covariates can abolish its impact on CV prognosis.

Intraoperative intrasac thrombin injection to prevent type II endoleak after endovascular abdominal aortic aneurysm repair.

Purpose: To report a prospective, nonrandomized pilot study to determine whether fibrin glue aneurysm sac embolization at the time of endovascular aneurysm repair (EVAR) is a safe and effective procedure to primarily prevent type II endoleaks. Methods: Between June 2003 and December 2005, 84 consecutive patients (79 men; mean age 73.8±7.8 years, range 64–86) with degenerative infrarenal abdominal aortic aneurysm underwent EVAR with bifurcated stent-grafts and fibrin glue injection into the aneurysm sac at the conclusion of the endovascular procedure. A total of 424 imaging studies and 348 visits were recorded during the study period and reviewed. Results: Selective catheterization of the aneurysm sac and fibrin glue injection immediately after initial stent-graft deployment was successful in 83 (99%) of 84 cases; there was one failure to access the excluded aneurysm sac due to severe iliac artery calcification. The estimated primary and assisted clinical success rates at 2 years were 91.3% and 98.8%, respectively, but the major findings were the low rate of delayed type II endoleak (2.4%) and the statistically significant decrease in the maximum transverse aneurysm diameter (50.40±6.70 versus 42.03±6.50 mm, p=0.0001) at follow-up. In addition, of 31 patients available for 24-month follow-up, 14 (45.2%) patients showed a reduction in maximum transverse aneurysm diameter by ≥5 mm; 16 (51.6%) patients had no significant changes, whereas only 1 patient showed a >5-mm enlargement. Conclusion: This clot engineering approach to aneurysm sac embolization at the time of endografting appears to be safe and may spare the patient a repeated catheter-based intervention or surgical procedure.

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients

Objective.  To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients.

Hyperhomocysteinemia Is Inversely Related With Left Ventricular Ejection Fraction and Predicts Cardiovascular Mortality in High-Risk Coronary Artery Disease Hypertensives

Objective— The purpose of this study was to investigate the relationship of plasma homocysteine (tHcy) levels with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) in high-risk patients undergoing coronary angiography for suspected CAD. Methods and Results— In 936 consecutive patients, we measured LVEF, tHcy, folate levels, and quantified CAD with a modified Duke Index score. We also genotyped patients at the methylen-tetrahydrofolate-reductase 677C→T polymorphism. Hyperhomocysteinemia (HHcy) was defined as tHcy levels ≥15.46 &mgr;mol/L; total and cardiovascular mortality was assessed at follow-up that lasted 43 months (median). CAD was confirmed in 75% of patients and ruled out in the rest (non-CAD group). No relationship of HHcy with either arterial hypertension or the CAD score was found. In contrast, there was a significant inverse relationship of tHcy with LVEF in arterial hypertensive but not in normotensive patients, regardless of previous myocardial infarction. At logistic regression, HHcy was the strongest predictor (P=0.001) of a low (<40%) LVEF, followed by type 2 diabetes mellitus and cigarette smoking. At follow-up, HHcy significantly predicted cardiovascular mortality but only in the arterial hypertension subgroup. Conclusions— In arterial hypertensive but not in normotensive patients, HHcy predicts cardiovascular mortality and a low LVEF, independent of CAD and history of myocardial infarction.

Aneurysm Sac “Thrombization” and Stabilization in EVAR: A Technique to Reduce the Risk of Type II Endoleak

Purpose: To evaluate the reduction in type II endoleak risk after introducing a new prevention method, “thrombization” or clotting of the aneurysm sac, during endovascular aneurysm repair (EVAR) versus the standard EVAR technique. Methods: From September 1999 to December 2008, 469 consecutive patients underwent EVAR for AAA at our institution. In 2003, the injection of fibrin glue with or without microcoils into the aneurysm sac was added to the EVAR treatment plan (“thrombization” technique). Patients who did not meet the inclusion criterion (at least 1-year follow-up imaging) were censored at the end of 2007, leaving 404 patients eligible for the study: 224 patients (210 men; mean age 71.9±8.5 years, range 25–88) undergoing EVAR alone from September 1999 to May 2003 (group 1)compared to 180 patients (161 men; mean age 72.6±8 years, range 46–89) who underwent EVAR + thrombization from June 2003 to December 2006 (group 2). Results: The 2 treatment groups were similar with regard to aneurysm morphology. No allergic or anaphylactic reactions were encountered related to the fibrin glue. Over median follow-up times of 72 months in group 1 and 26 months in group 2, there were 34 (15.2%) endoleaks in group 1 versus 4 (2.2%) in group 2 (p<0.0001). The incidence of type II endoleak was 0.25/100 person-months for group 1 versus 0.07/100 person-months for group 2. The preventive sac thrombization technique was significantly associated with a reduced risk of type II endoleak (HR 0.13, 95% CI 0.05 to 0.36; p<0.0001) regardless of the type of stent-graft fixation (infrarenal versus suprarenal). Conclusion: The preventive method of intrasac “thrombization” using fibrin glue injection with or without the insertion of coils proves to be a simple, low cost, safe, and effective technique to significantly reduce the risk of type II endoleaks irrespective of the endograft used.

Intracardiac echocardiography during catheter-based procedures: ultrasound system, examination technique, and image presentation.

A detailed understanding of the anatomic structures of both atria is mandatory for successful catheter‐based interventional techniques. Some of the drawbacks of transthoracic and transesophageal echocardiography can be overcome by intracardiac echocardiography (ICE). We present our ICE experience based on 70 out of 186 patients who were included in a multicenter registry of transcatheter interatrial communication closures. The ultrasound catheter was a 9‐Fr, 9 MHZ monoplane probe (Ultra ICE catheter) compatible with the motor drive unit and imaging console of the Clear View Ultra. Four slice selections in the axial plane and only one in the sagittal plane were needed in order to obtain a comprehensive guide to ICE interrogation. Their intracardiac ultrasound imaging presentation is an essential and nontrivial step. The anatomic coordinate system was maintained identical to a tomographic imaging plane as follows: Left/right and anterior/posterior in the axial planes and superior/inferior and anterior/posterior in the sagittal plane. In order to identify the imaging coordinates, two specific anatomic landmarks were used. The first one was the crista terminalis (at 10 o′clock) and the second one was the right atrial auricle (at 12 o′clock). Once the ultrasound images were orientated, their interpretation and spatial reconstruction were straightforward. In conclusion, a standardized ICE examination allows for a comprehensive evaluation of the right atrial anatomy and may be helpful in guiding therapeutic catheter‐based interventions. The major clinical advantages of ICE include optimal contrast between soft‐tissue structures, limited fluoroscopic exposure time, and good patient acceptance, thus avoiding general anesthesia.

Fibrin glue aneurysm sac embolization at the time of endografting.

Purpose: To describe the procedural details for primary prevention of type II endoleak with fibrin glue injection into the aneurysm sac at the time of endografting. Technique: After deployment of the main stent-graft component, the angiographic pigtail catheter is withdrawn, leaving the 0.035-inch standard guidewire between the endograft and the native aorta. Through a brachial-femoral arterial guidewire loop, an 11-cm-long, 6-F introducer is advanced over the wire into the contralateral iliac artery. After deployment of the contralateral iliac extension, a 23-cm, 5-F sheath is advanced over the wire into the aneurysm sac. The wire and vessel dilator are removed, leaving the cannula in the sac. To prevent distal embolization of the sealant, a balloon is inflated in the contralateral limb to secure it to the native vessel before 5 mL of fibrin sealant are injected into the sac via a double-syringe delivery system inserted through the sheath. The balloon is left in place for 1 minute after sealant injection. In 64 consecutive patients in whom this technique has been used, sac embolization has been successful. There have been no intraoperative complications or in-hospital mortality. Over a mean follow-up of 9.3±4.4 months (range 1–18), only 1 lumbar endoleak has been detected on surveillance imaging. Conclusions: This preventive strategy appears to be an effective approach and the best therapeutic choice for preventive management of type II endoleak.

Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.

Objective The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. Design A prospective study cohort. Setting A tertiary centre. Patients Inclusion criteria: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. Exclusion criteria: acute myocardial infarction and vitamin supplementation. Main outcome measure(s) We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C→T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 μmol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. Results Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan–Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. Conclusion Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.

Transcatheter Amplatzer duct occluder closure of direct right pulmonary to left atrium communication.

Although rare, a congenital direct communication between pulmonary artery and left atrium can present a paradoxical embolism in adults. In our case, diagnosis was first made on contrast transcranial Doppler with Valsalva maneuver and subsequently confirmed by intracardiac echocardiography and selective pulmonary angiography. Successful catheter‐based closure using Amplatzer duct occluder device resulted in definitive exclusion of the source of paradoxical embolism. Cathet Cardiovasc Intervent 2003;58:107–110.